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Abstract
BackgroundThe aim of this study was to investigate the effect of Iguratimod (T-614) on rat knee osteoarthritis (KOA) and further to explore its underlying mechanism.MethodsIn this study, papain-induced KOA model was constructed. Hematoxylin and eosin (H&E) staining was conducted to observe the pathological changes of cartilage tissue and Mankin scoring principle was used for quantitative scoring. Transmission electron microscopy (TEM) was applied to observe the ultrastructure of cartilage tissue. ELISA was used to measure the levels of matrix metalloproteinase 13 (MMP-13) and inflammatory factors (interleukin (IL)-6 and tumor necrosis factor a (TNF-a)) in serum. RT-qPCR and immunohistochemistry were conducted to detect mRNA expression and protein expression of key genes in Wnt/β-catenin pathway.ResultsH&E, Mankin scoring, and TEM data confirmed that compared with model group, T-614 significantly improved the degeneration of articular cartilage. Besides, we observed that low, middle, and high doses of T-614 could decrease the levels of MMP13, TNF-α, and IL-6 in serum to different degrees. Mechanically, T-614 downregulated the mRNA and protein expression of β-catenin and MMP13 in cartilage tissue via a dose-dependent manner, and on the contrary upregulated the mRNA and protein expression of glucogen synthase kinase-3 beta (GSK-3β).ConclusionOur results suggested that T-614 can reduce the level of its downstream target gene MMP-13 and downregulate the expression of inflammatory cytokines TNF-α and IL-6 by regulating the Wnt/β-catenin signaling pathway, thereby inhibiting joint inflammation and controlling KOA degeneration of articular cartilage.
Highlights
The aim of this study was to investigate the effect of Iguratimod (T-614) on rat knee osteoarthritis (KOA) and further to explore its underlying mechanism
In the T-614 high-dose group, we found that the cartilage structure was significantly improved compared with the model group and the T-614 low– middle-dose group, which showed some irregular cartilage fissures, occasionally swelling of chondrocytes and complete tide lines
To more accurately observe the changes of cartilage tissue in each group, Mankin score was used for quantitative scoring
Summary
The aim of this study was to investigate the effect of Iguratimod (T-614) on rat knee osteoarthritis (KOA) and further to explore its underlying mechanism. Knee osteoarthritis (KOA) is an inflammatory disease occurring in human joints and their surrounding tissues. Surgical treatment has a good effect in improving patients’ pain, nearly half of patients still have long-term pain after surgery, and some patients need a second surgery [7, 8]. It was observed that T-614 significantly improved rheumatoid arthritis symptoms [11]. Du et al revealed that T-614 can improve the symptoms of rheumatoid arthritis, and prevent bone destruction [12]. The research on the mechanism of T-614 acting on cartilage tissue has been poorly elucidated
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